Cells as the living units of the body

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Cells as the living units of the body

  1. 1. ‫بسم اللة الرحمن الرحيم‬ ‫‪Dr Alamzeb Khan‬‬ ‫1‬
  2. 2. 2
  3. 3. Physiology Science that describes how organisms FUNCTION and survive in continually changing environments   Dr Alamzeb Khan 3
  4. 4. CELL:DEFINITION: Cell is the structure and functional unit of all life…. Living components is called protoplasm Discovery: For the first time by Robert Hook Robert Brown discovered the nucleus in plant cell T.Schwan discovered animal cell for the first time
  5. 5. Cells as the Living Units of the BodyCELLULAR LEVEL - cells are the basic structural andfunctional units of the human body & there are many differenttypes of cells (e.g., muscle, nerve, blood, and so on) Dr Alamzeb Khan 5
  6. 6. Basic Characteristics In all cells, oxygen reacts with carbohydrate, fat, and protein to release the energy required for cell function. General chemical mechanisms for changing nutrients into energy are basically the same in all cells All cells deliver end products of their chemical reactions into the surrounding fluids. Almost all cells have the ability to reproduce their own kind Dr Alamzeb Khan 6
  7. 7.  TISSUE LEVEL - a tissue is a group of cells that perform a specific function .The basic types of tissues in the human body include epithelial, muscle, nervous, and connective tissues Dr Alamzeb Khan 7
  8. 8.  ORGAN LEVEL - an organ consists of 2 or more tissues that perform a particular function (e.g., heart, liver, stomach, and so on) SYSTEM LEVEL - an association of organs that have a common function; the major systems in the human body include digestive, nervous, endocrine, circulatory, respiratory, urinary, and reproductive. Dr Alamzeb Khan 8
  9. 9.  There are two types of cells that make up all living things on earth: prokaryotic Eukaryotic. Prokaryotic cells, like bacteria, have no nucleus, while eukaryotic cells, like those of the human body, do. Human cell is enclosed by a cell, or plasma, membrane. Enclosed by that membrane is the cytoplasm (with associated organelles) plus a nucleus. Dr Alamzeb Khan 9
  10. 10.  Two major parts of the cell Organization of the are the nucleus and the Cell cytoplasm The nucleus is separated from the cytoplasm by a nuclear membrane, and the cytoplasm is separated from the surrounding fluids by a cell membrane, also called the plasma membrane The different substances that make up the cell are collectively called protoplasm. Protoplasm is composed mainly of five basic substances: water, electrolytes, proteins, lipids, and carbohydrates. Dr Alamzeb Khan 10
  11. 11. Cell, or Plasma, membrane - encloses every human cell  Structure - 2 primary building blocks include protein (about 60% of the membrane) and lipid, or fat (about 40% of the membrane). The primary lipid is called phospholipid, and molecules of phospholipid form a phospholipid bilayer (two layers of phospholipid molecules). This bilayer forms because the two ends of phospholipid molecules have very different characteristics: one end is polar (or hydrophilic) and one (the hydrocarbon tails below) is non-polar (or hydrophobic): Dr Alamzeb Khan 11
  12. 12.  The lipid layer in the middle of the membrane is impermeable to the usual water-soluble substances, such as ions, glucose , and urea fat-soluble substances, such as oxygen, carbon dioxide, and alcohol, can penetrate this portion of the membrane with ease. Dr Alamzeb Khan 12
  13. 13.  Cholesterol molecules are dissolved in the The cholesterol bilayer of the membrane. determine the degree of permeability (or impermeability) of the bilayer to water- soluble constituents. Cholesterol controls much of the fluidity of the membrane as Dr Alamzeb Khan 13
  14. 14. Cell Membrane Proteins. Proteins are globular masses floating in the lipid bilayer. most of which are glycoproteins. Two types of proteins occur: integral proteins that protrude all the way through the membrane, peripheral proteins that are attached only to one surface of the membrane and do not penetrate all the way through. Dr Alamzeb Khan 14
  15. 15. Membrane Carbohydrates Membrane carbohydrates occur in combination with proteins or lipids in the form of glycoproteins or glycolipids. most of the integral proteins are glycoproteins, and about one tenth of the membrane lipid molecules are glycolipids. The "glyco" portions of these molecules almost invariably protrude to the outside of the cell. Dr Alamzeb Khan 15
  16. 16.  Many other carbohydrate compounds, called proteoglycans-which are mainly carbohydrate substances bound to small protein cores-are loosely attached to the outer surface of the cell as well. Thus, the entire outside surface of the cell often has a loose carbohydrate coat called the glycocalyx. Dr Alamzeb Khan 16
  17. 17. Functions of membrane include: supporting and retaining the cytoplasm being a selective barrier  The cell is separated from its environment and needs to get nutrients in and waste products out.  Some molecules can cross the membrane without assistance, most cannot.  Water, non-polar molecules and some small polar molecules can cross.  Non-polar molecules penetrate by actually dissolving into the lipid bilayer.  Most polar compounds such as amino acids, organic acids and inorganic salts are not allowed entry, but instead must be specifically transported across the membrane by proteins. Dr Alamzeb Khan 17
  18. 18.  Many of the proteins in the membrane function Transport to help carry out selective transport. These proteins typically span the whole membrane, making contact with the outside environment and the cytoplasm. They often require the expenditure of energy to help compounds move across the membrane Dr Alamzeb Khan 18
  19. 19. Cytoplasm and organelles Cytoplasm consists of a gelatinous solution and contains microtubules (which serve as a cells cytoskeleton) organelles (literally little organs) Without one of the organelles, the mitochondria, more than 95 per cent of the cells energy release from nutrients would cease immediately. Dr Alamzeb Khan 19
  20. 20. Organelles Dispersed in the cytoplasm are five especially important organelles: the endoplasmic reticulum, the Golgi apparatus, mitochondria, lysosomes, and peroxisomes. Dr Alamzeb Khan 20
  21. 21. Endoplasmic Reticulum a network of tubular and flat vesicular structures in the cytoplasm; The tubules and vesicles interconnect with one another. Dr Alamzeb Khan 21
  22. 22.  The space inside the tubules and vesicles is filled with endoplasmic matrix, a watery medium that is different from the fluid in the cytosol outside the endoplasmic reticulum. Electron micrographs show that the space inside the endoplasmic reticulum is connected with the space between the two membrane surfaces of the nuclear membrane. Dr Alamzeb Khan 22
  23. 23.  Substances formed in some parts of the cell enter the space of the endoplasmic reticulum and are then conducted to other parts of the cell. Also, the vast surface area of this reticulum and the multiple enzyme systems attached to its membranes provide machinery for a major share of the metabolic functions of the cell. Dr Alamzeb Khan 23
  24. 24. Ribosomes and the Granular Endoplasmic Reticulum. Attached to the outer surfaces of many parts of the endoplasmic reticulum are large numbers of minute granular particles called ribosomes. Where these are present, the reticulum is called the granular endoplasmic reticulum. The ribosomes are composed of a mixture of RNA and proteins, and they function to synthesize new protein molecules inAlamzeb Khan Dr 24
  25. 25. Agranular Endoplasmic Reticulum. Part of the endoplasmic reticulum has no attached ribosomes. This part is called the agranular, or smooth, endoplasmic reticulum. The agranular reticulum functions for the synthesis of lipid substances and for other processes of the cells promoted by intrareticular enzymes. Dr Alamzeb Khan 25
  26. 26.  The Golgi apparatusis closely related to the Golgi Apparatus endoplasmic reticulum. It has membranes similar to those of the agranular endoplasmic reticulum. It usually is composed of four or more stacked layers of thin, flat, enclosed vesicles lying near one side of the nucleus. This apparatus is prominent in secretory cells, where it is located on the side of the cell from which the secretory substances are extruded.Alamzeb Khan Dr 26
  27. 27.  small "transport vesicles" (also called endoplasmic reticulum vesicles, or ER vesicles) continually pinch off from the endoplasmic reticulum and shortly thereafter fuse with the Golgi apparatus. In this way, substances entrapped in the ER vesicles are transported from the endoplasmic reticulum to the Golgi apparatus. The transported substances are then processed in the Golgi apparatus to form lysosomes, Dr Alamzeb Khan 27
  28. 28. Lysosome Lysosomes, are vesicular organelles that form by s breaking off from the Golgi apparatus and then dispersing throughout the cytoplasm. The lysosomes provide an intracellular digestive system that allows the cell to digest (1) damaged cellular structures, (2) food particles that have been ingested by the cell, and (3) unwanted matter such as bacteria. Dr Alamzeb Khan 28
  29. 29. Peroxisomes Peroxisomes Peroxisomes Peroxisomes are similar physically to lysosomes, but they are different in two important ways. First, they are formed by self-replication Second, they contain oxidases rather than hydrolases. capable of combining oxygen with hydrogen ions to form hydrogen peroxide (H2O2). a highly oxidizing substance Dr Alamzeb Khan 29
  30. 30. Secretory Vesicles Almost all such secretory substances are formed by the endoplasmic reticulum-Golgi apparatus system and are then released from the Golgi apparatus into the cytoplasm in the form of storage vesicles called secretory vesicles or secretory granules. these vesicles store protein proenzymes Dr Alamzeb Khan 30
  31. 31. Mitochondria The mitochondria, are called the "powerhouses" of the cell. Without them, cells would be unable to extract enough energy from the nutrients, and essentially all cellular functions would cease. Mitochondria are present in all areas of each cells cytoplasm, but the total number per cell varies from less than a hundred up to several thousand Dr Alamzeb Khan 31
  32. 32. The basic structure of the mitochondrion composed mainly of two lipid bilayer-protein membranes: an outer membrane and an inner membrane. Many infoldings of the inner membrane form shelves onto which oxidative enzymes are attached. In addition, the inner cavity of the mitochondrion is filled with a matrix that contains large quantities of dissolved enzymes that are necessary for extracting energy from nutrients. These enzymes operate in association with the oxidative enzymes on the shelves to cause oxidation of the nutrients, thereby forming carbon dioxide and water and at the same time releasing energy. The liberated energy is used to synthesize a "high-energy" substance called adenosine triphosphate (ATP). ATP is then transported out of the mitochondrion, and it diffuses throughout the cell to release its own energy wherever it is needed for performing cellular functions Dr Alamzeb Khan 32
  33. 33. Filament and Tubular Structures of the Cell The fibrillar proteins of the cell are usually organized into filaments or tubules. These originate as precursor protein molecules synthesized by ribosomes in the cytoplasm. The precursor molecules then polymerize to form filaments. As an example, large numbers of actin filaments frequently occur in the outer zone of the cytoplasm, called the ectoplasm, to form an elastic support for the cell membrane. Dr Alamzeb Khan 33
  34. 34. Nucleus The nucleus is the control center of the cell. contains large quantities of DNA, Dr Alamzeb Khan 34
  35. 35. Nuclear Membrane The nuclear membrane, also called the nuclear envelope, is actually two separate bilayer membranes, one inside the other. The outer membrane is continuous with the endoplasmic reticulum of the cell cytoplasm, and the space between the two nuclear membranes is also continuous with the space inside the endoplasmic reticulum Dr Alamzeb Khan 35
  36. 36. The nuclear membrane is penetrated by several thousand nuclear pores. Large complexes of protein molecules are attached at the edges of the pores so that the central area of each pore is only about 9 nanometers in diameter. Even this size is large enough to allow molecules up to 44,000 molecular weight to pass through with reasonable ease.Dr Alamzeb Khan 36
  37. 37.  Nucleoli The nuclei of most cells contain one or more highly staining structures called nucleoli. The nucleolus, it is simply an accumulation of large amounts of RNA and proteins of the types found in ribosomes. Dr Alamzeb Khan 37
  38. 38. Dr Alamzeb Khan 38
  39. 39. Dr Alamzeb Khan 39
  40. 40. Extracellular Fluid-The "Internal Environment" About 60 per cent of the adult human body is fluid, mainly a water solution of ions and other substances. Most of this fluid is inside the cells and is called intracellular fluid. One third is in the spaces outside the cells and is called extracellular fluid. All cells live in essentially the same environment-the extracellular fluid. For this reason, the extracellular fluid is also called the internal environment of the body, or the milieu intérieur, Dr Alamzeb Khan 40
  41. 41. Differences Between Extracellular and Intracellular Fluids. Dr Alamzeb Khan 41
  42. 42. Homeostasis Maintenance of nearly constant conditions in the internal environment lungs provide oxygen to the extracellular fluid to replenish the oxygen used by the cells, kidneys maintain constant ion concentrations, Gastrointestinal system provides nutrients. Dr Alamzeb Khan 42
  43. 43. Physical Structure of the Cell Cell contains highly organized physical structures, called intracellular organelles. Without one of the organelles, the mitochondria, more than 95 per cent of the cells energy release from nutrients would cease immediately. Dr Alamzeb Khan 43
  44. 44. Dr Alamzeb Khan 44
  45. 45. Membranous Structures of the Cell Most organelles of the cell are covered by membranes composed primarily of lipids and proteins. These membranes include the cell membrane, nuclear membrane, membrane of the endoplasmic reticulum, and membranes of the mitochondria, lysosomes, and Golgi apparatus. Dr Alamzeb Khan 45
  46. 46. Cell Membrane The cell membrane (also called the plasma membrane), which envelops the cell, is a thin, pliable, elastic structure only 7.5 to 10 nanometers thick. It is composed almost entirely of proteins and lipids. The approximate composition is proteins, 55 per cent; phospholipids, 25 per cent; cholesterol, 13 per cent; other lipids, 4 per cent; and carbohydrates, 3 per cent. Dr Alamzeb Khan 46
  47. 47.  Its basic structure is a lipid bilayer, which is a thin, double-layered film of lipids-each layer only one Lipid molecule thick-that is continuous over the entire cell surface. Interspersed in this lipid film are large globular protein molecules. The basic lipid bilayer is composed of phospholipid molecules. One end of each phospholipid molecule is soluble in water; that is, it is hydrophilic. The other end is soluble only in fats; that is, it is hydrophobic. The phosphate end of the phospholipid is hydrophilic, and the fatty acid portion is hydrophobic. Dr Alamzeb Khan 47
  48. 48.  Because the hydrophobic portions of the phospholipid molecules are repelled by water but are mutually attracted to one another, they have a natural tendency to attach to one another in the middle of the membrane, The hydrophilic phosphate portions then constitute the two surfaces of the complete cell membrane, in contact with intracellular water on the inside of the membrane and extracellular water on the outside surface Dr Alamzeb Khan 48
  49. 49.  The lipid layer in the middle of the membrane is impermeable to the usual water-soluble substances, such as ions, glucose , and urea fat-soluble substances, such as oxygen, carbon dioxide, and alcohol, can penetrate this portion of the membrane with ease. Dr Alamzeb Khan 49
  50. 50. The cholesterol cholesterol molecules are dissolved in the bilayer of the membrane. determine the degree of permeability (or impermeability) of the bilayer to water-soluble constituents. Cholesterol controls much of the fluidity of the membrane as well. Dr Alamzeb Khan 50
  51. 51.  Many of the integral proteins provide structural channels (or pores) through which water molecules and water-soluble substances, especially ions, can diffuse between the extracellular and intracellular fluids. These protein channels also have selective properties that allow preferential diffusion of some substances over others. Dr Alamzeb Khan 51
  52. 52.  Other integral proteins act as carrier proteins for transporting substances that otherwise could not penetrate the lipid bilayer. Sometimes these even transport substances in the direction opposite to their natural direction of diffusion, which is called "active transport." Still others act as enzymes. Dr Alamzeb Khan 52
  53. 53.  Integral membrane proteins serve as receptors for water- soluble chemicals, such as peptide hormones, that do not easily penetrate the cell membrane. Dr Alamzeb Khan 53
  54. 54. Membrane Carbohydrates Membrane carbohydrates occur in combination with proteins or lipids in the form of glycoproteins or glycolipids. most of the integral proteins are glycoproteins, and about one tenth of the membrane lipid molecules are glycolipids. The "glyco" portions of these molecules almost invariably protrude to the outside of the cell. Many other carbohydrate compounds, called proteoglycans-which are mainly carbohydrate substances bound to small protein cores-are loosely attached to the outer surface of the cell as well. Thus, the entire outside surface of the cell often has a loose carbohydrate coat called the glycocalyx. Dr Alamzeb Khan 54
  55. 55.  The carbohydrate moieties attached to the outer surface of the cell have several important functions: (1) Many of them have a negative electrical charge, which gives most cells an overall negative surface charge that repels other negative objects. (2) The glycocalyx of some cells attaches to the glycocalyx of other cells, thus attaching cells to one another. (3) Many of the carbohydrates act as receptor substances for binding hormones, such as insulin; when bound, this combination activates attached internal proteins that, in turn, activate a cascade of intracellular enzymes. (4) Some carbohydrate moieties enter into immune reactions Dr Alamzeb Khan 55
  56. 56. Cytoplasm and Its Organelles The cytoplasm is filled with both minute and large dispersed particles and organelles. The clear fluid portion of the cytoplasm in which the particles are dispersed is called cytosol; this contains mainly dissolved proteins, electrolytes, and glucose . Dr Alamzeb Khan 56
  57. 57. Dr Alamzeb Khan 57
  58. 58. Endoplasmic Reticulum a network of tubular and flat vesicular structures in the cytoplasm; The tubules and vesicles interconnect with one another. their walls are constructed of lipid bilayer membranes that contain large amounts of proteins, similar to the cell membrane. Dr Alamzeb Khan 58
  59. 59.  The space inside the tubules and vesicles is filled with endoplasmic matrix, a watery medium that is different from the fluid in the cytosol outside the endoplasmic reticulum. Electron micrographs show that the space inside the endoplasmic reticulum is connected with the space between the two membrane surfaces of the nuclear membrane. Dr Alamzeb Khan 59
  60. 60.  Substances formed in some parts of the cell enter the space of the endoplasmic reticulum and are then conducted to other parts of the cell. Also, the vast surface area of this reticulum and the multiple enzyme systems attached to its membranes provide machinery for a major share of the metabolic functions of the cell. Dr Alamzeb Khan 60
  61. 61. Ribosomes and the Granular Endoplasmic Reticulum. Attached to the outer surfaces of many parts of the endoplasmic reticulum are large numbers of minute granular particles called ribosomes. Where these are present, the reticulum is called the granular endoplasmic reticulum. The ribosomes are composed of a mixture of RNA and proteins, and they function to synthesize new protein molecules in the cell Dr Alamzeb Khan 61
  62. 62. Agranular Endoplasmic Reticulum. Part of the endoplasmic reticulum has no attached ribosomes. This part is called the agranular, or smooth, endoplasmic reticulum. The agranular reticulum functions for the synthesis of lipid substances and for other processes of the cells promoted by intrareticular enzymes. Dr Alamzeb Khan 62
  63. 63. Golgi Apparatus The Golgi apparatusis closely related to the endoplasmic reticulum. It has membranes similar to those of the agranular endoplasmic reticulum. It usually is composed of four or more stacked layers of thin, flat, enclosed vesicles lying near one side of the nucleus. This apparatus is prominent in secretory cells, where it is located on the side of the cell from which the secretory substances are extruded. Dr Alamzeb Khan 63
  64. 64.  small "transport vesicles" (also called endoplasmic reticulum vesicles, or ER vesicles) continually pinch off from the endoplasmic reticulum and shortly thereafter fuse with the Golgi apparatus. In this way, substances entrapped in the ER vesicles are transported from the endoplasmic reticulum to the Golgi apparatus. The transported substances are then processed in the Golgi apparatus to form lysosomes, secretory vesicles, and other cytoplasmic components Dr Alamzeb Khan 64
  65. 65.  Lysosomes, are vesicular organelles that form by breaking off from the Golgi apparatus and then dispersing throughout the cytoplasm. Lysosome The lysosomes provide an intracellular digestive system that allows the cell to digest (1) damaged cellular structures, (2) food particles that have s been ingested by the cell, and (3) unwanted matter such as bacteria. The lysosome is quite different in different types of cells, but it is usually 250 to 750 nanometers in diameter. It is surrounded by a typical lipid bilayer membrane and is filled with large numbers of small granules 5 to 8 nanometers in diameter, which are protein aggregates of as many as 40 different hydrolase (digestive) enzymes. A hydrolytic enzyme is capable of splitting an organic compound into two or more parts by combining hydrogen from a water molecule with one part of the compound and combining the hydroxyl portion of the water molecule with the other part of the compound. For instance, protein is hydrolyzed to form amino acids , glycogen is hydrolyzed to form glucose , and lipids are hydrolyzed to form fatty acids and glycerol. Dr Alamzeb Khan 65
  66. 66. Peroxisomes Peroxisomes Peroxisomes Peroxisomes are similar physically to lysosomes, but they are different in two important ways. First, they are believed to be formed by self-replication (or perhaps by budding off from the smooth endoplasmic reticulum) rather than from the Golgi apparatus. Second, they contain oxidases rather than hydrolases. Several of the oxidases are capable of combining oxygen with hydrogen ions derived from different intracellular chemicals to form hydrogen peroxide (H2O2). Hydrogen peroxide is a highly oxidizing substance and is used in association with catalase, another oxidase enzyme present in large quantities in peroxisomes, to oxidize many substances that might otherwise be poisonous to the cell. For instance, about half the alcohol a person drinks is detoxified by the peroxisomes of the liver cells in this manner Dr Alamzeb Khan 66
  67. 67. Secretory Vesicles . Almost all such secretory substances are formed by the endoplasmic reticulum-Golgi apparatus system and are then released from the Golgi apparatus into the cytoplasm in the form of storage vesicles called secretory vesicles or secretory granules. these vesicles store protein proenzymes Dr Alamzeb Khan 67
  68. 68. Mitochondria The mitochondria, are called the "powerhouses" of the cell. Without them, cells would be unable to extract enough energy from the nutrients, and essentially all cellular functions would cease. Mitochondria are present in all areas of each cells cytoplasm, but the total number per cell varies from less than a hundred up to several thousand Dr Alamzeb Khan 68
  69. 69. The basic structure of the mitochondrion composed mainly of two lipid bilayer-protein membranes: an outer membrane and an inner membrane. Many infoldings of the inner membrane form shelves onto which oxidative enzymes are attached. In addition, the inner cavity of the mitochondrion is filled with a matrix that contains large quantities of dissolved enzymes that are necessary for extracting energy from nutrients. These enzymes operate in association with the oxidative enzymes on the shelves to cause oxidation of the nutrients, thereby forming carbon dioxide and water and at the same time releasing energy. The liberated energy is used to synthesize a "high-energy" substance called adenosine triphosphate (ATP). ATP is then transported out of the mitochondrion, and it diffuses throughout the cell to release its own energy wherever it is needed for performing cellular functions Dr Alamzeb Khan 69
  70. 70. Filament and Tubular Structures of the Cell The fibrillar proteins of the cell are usually organized into filaments or tubules. These originate as precursor protein molecules synthesized by ribosomes in the cytoplasm. The precursor molecules then polymerize to form filaments. As an example, large numbers of actin filaments frequently occur in the outer zone of the cytoplasm, called the ectoplasm, to form an elastic support for the cell membrane. Dr Alamzeb Khan 70
  71. 71. Nucleus The nucleus is the control center of the cell. contains large quantities of DNA, which are the genes. The genes determine the characteristics of the cells proteins, including the structural proteins, as well as the intracellular enzymes that control cytoplasmic and nuclear activities. The genes also control and promote reproduction of the cell itself. Dr Alamzeb Khan 71
  72. 72. Nuclear Membrane The nuclear membrane, also called the nuclear envelope, is actually two separate bilayer membranes, one inside the other. The outer membrane is continuous with the endoplasmic reticulum of the cell cytoplasm, and the space between the two nuclear membranes is also continuous with the space inside the endoplasmic reticulum Dr Alamzeb Khan 72
  73. 73. The nuclear membrane is penetrated by several thousand nuclear pores. Large complexes of protein molecules are attached at the edges of the pores so that the central area of each pore is only about 9 nanometers in diameter. Even this size is large enough to allow molecules up to 44,000 molecular weight to pass through with reasonable ease.Dr Alamzeb Khan 73
  74. 74.  Nucleoli and Formation of Ribosomes The nuclei of most cells contain one or more highly staining structures called nucleoli. The nucleolus, unlike most other organelles discussed here, does not have a limiting membrane. Instead, it is simply an accumulation of large amounts of RNA and proteins of the types found in ribosomes. The nucleolus becomes considerably enlarged when the cell is actively synthesizing proteins. Formation of the nucleoli (and of the ribosomes in the cytoplasm outside the nucleus) begins in the nucleus. First, specific DNA genes in the chromosomes cause RNA to be synthesized. Some of this is stored in the nucleoli, but most of it is transported outward through the nuclear pores into cytoplasm. Here, it is used in conjunction with specific proteins to assemble "mature" ribosomes that play an essential role in forming cytoplasmic proteins Dr Alamzeb Khan 74
  75. 75. Dr Alamzeb Khan 75

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